Evidence Grade A — Regulatory approved. 751 published studies. 72 registered clinical trials.
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Pasireotide (sold as Signifor) is the first and only medication approved specifically for Cushing's disease — a serious condition caused by a pituitary tumour that floods the body with the stress hormone cortisol, leading to weight gain, high blood sugar, bone thinning, and muscle weakness. It is also approved for acromegaly when other somatostatin treatments have not worked well enough.
Pasireotide is also known by these brand and alternate names:
751 published studies: 565 human, 41 animal, 67 in-vitro, 242 reviews
Pasireotide is marketed as Signifor for Cushing's disease (approved December 2012) and Signifor LAR for acromegaly (approved December 2014). In Cushing's disease, approximately 26% of patients achieved normal cortisol levels after six months of treatment. In acromegaly, pasireotide LAR achieved hormone control in 31.3% of patients versus 19.2% for octreotide LAR.
The main limitation of pasireotide is a significant impact on blood sugar — diabetes occurred in 19–26% of patients in clinical trials, substantially higher than with octreotide or lanreotide. This is because the broader receptor profile also suppresses insulin release more strongly. As a result, pasireotide is typically reserved for patients who have not responded adequately to other somatostatin analogues, rather than used as a first-line treatment.
While octreotide and lanreotide mainly target two of the five somatostatin receptors, pasireotide binds to four of them. This broader coverage is critical for treating Cushing's disease because the pituitary tumours that cause this condition predominantly express the receptor type (SST5) that older somatostatin analogues barely reach. By targeting SST5 with high affinity, pasireotide can directly suppress the excess cortisol-stimulating hormone (ACTH) that these tumours produce.
In Cushing's disease, approximately 26% of patients achieved normal cortisol levels after six months of treatment — a modest response rate, but meaningful given the severity of the condition and the limited alternatives available when surgery does not cure it. For acromegaly, pasireotide showed superiority over octreotide in hormone control (31% versus 19%). The significant drawback is its impact on blood sugar. Pasireotide suppresses insulin release more aggressively than older somatostatin drugs, and new-onset diabetes occurred in 19-26% of patients in clinical trials. This makes blood sugar management a co-treatment concern and limits pasireotide to second-line use in most cases. Oral cortisol synthesis inhibitors (like osilodrostat) have emerged as alternative non-surgical approaches for Cushing's disease.
PeptideTrace tracks 72 registered clinical trials for Pasireotide sourced from ClinicalTrials.gov.
Compassionate Use of SOM230 for Hyperinsulinemic/Hypoglycemia
An Open-label, Multi-center, Expanded Treatment Protocol of Pasireotide LAR in Patients With Acromegaly
Study in Healthy Subjects to Investigate the Relative Bioavailability and Safety of Pasireotide After Single Subcutaneous Dose Administration Using a Reusable ServoPen With Cartridge as Compared to Administration Using a Syringe Drawn From an Ampule
Effects of Pasireotide Lar Therapy on Bone Metabolism
Pasireotide as Maintenance Treatment in Synovial Sarcoma and Desmoplastic Small Round Cell Tumor
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Pasireotide is a synthetic cyclohexapeptide (6 amino acids) somatostatin analogue with a broader receptor binding profile than octreotide or lanreotide. It is the first pituitary-directed medical therapy for Cushing's disease.
Pasireotide binds SST1, SST2, SST3, and SST5 receptors. Its affinity for SST5 is approximately 40-fold higher than octreotide, which is critical because corticotroph adenomas (causing Cushing's disease) predominantly express SST5. This multi-receptor binding profile also provides enhanced GH suppression in some acromegaly patients who are resistant to SST2-selective agents. However, SST5-mediated suppression of insulin and incretin secretion produces significant hyperglycemia.
Pasireotide is marketed as Signifor (SC BID, approved December 14, 2012 for Cushing's disease) and Signifor LAR (IM monthly, approved December 15, 2014 for acromegaly). In the C2305 acromegaly trial, pasireotide LAR achieved GH/IGF-1 biochemical control in 31.3% versus 19.2% for octreotide LAR (P=0.007). In Cushing's disease (Phase 3, N=162), 26.3% achieved urinary free cortisol normalization at 6 months. Major concern: hyperglycemia in 57–73% of patients (diabetes in 26% vs 4% with octreotide), requiring proactive glucose management.
Linaclotide is marketed as Linzess (approved August 2012). It is taken as a daily oral capsule on an empty stomach, at least 30 minutes before the first meal. The recommended dose is 290 mcg for IBS-C and 72 or 145 mcg for chronic constipation. In clinical trials, approximately 34% of IBS-C patients met the composite improvement endpoint compared to 17% on placebo. Diarrhoea is the most common side effect (approximately 20%) and the leading reason for discontinuation. Linaclotide has a boxed warning against use in children under 6 years due to deaths in young mice, though no such events have been reported in humans. It competes with plecanatide (which targets the same pathway) and other IBS-C treatments.
Elamipretide (Forzinity) was approved by the FDA for Barth syndrome based on the TAZPOWER trial. The randomised crossover phase (12 patients) did not meet its primary endpoints, but the open-label extension (168 weeks) demonstrated durable improvements in walking distance and muscle strength that formed the basis for approval. Barth syndrome affects approximately 1 in 300,000–400,000 births. A larger Phase III trial in primary mitochondrial myopathy (218 patients, MMPOWER-3) did not meet its primary endpoint, and the drug was not approved for that broader indication. Elamipretide remains approved exclusively for Barth syndrome. See also SS-31 (#158) for the research compound context.
Glucagon has been available as an emergency injection since the 1960s and remains the standard rescue treatment for severe hypoglycaemia. Recent innovation has focused on making it easier to administer in emergencies. Baqsimi, approved in 2019, was the first needle-free option as a nasal powder. Gvoke, also approved in 2019, eliminated the need to mix and reconstitute the medication before injection — a significant advance since severe hypoglycaemia often impairs the ability to follow complex preparation steps. Dasiglucagon (Zegalogue), a next-generation stable liquid glucagon approved in 2021, further improved on the convenience of rescue administration. Beyond emergency rescue, glucagon's receptor is now a major research target — dual and triple agonists combining glucagon receptor activity with GLP-1 (such as survodutide and retatrutide) are in advanced clinical trials for obesity and metabolic disease.
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